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MedKoo Cat#: 540274 | Name: Lonidamine
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Lonidamine is an inhibitor of hexokinase and aerobic glycolysis. It increases lifespan in Caenorhabditis elegans, inhibits growth of Trypanosoma, and decreases sperm count and testosterone levels.

Chemical Structure

Lonidamine
Lonidamine
CAS#50264-69-2

Theoretical Analysis

MedKoo Cat#: 540274

Name: Lonidamine

CAS#: 50264-69-2

Chemical Formula: C15H10Cl2N2O2

Exact Mass: 320.0119

Molecular Weight: 321.16

Elemental Analysis: C, 56.10; H, 3.14; Cl, 22.08; N, 8.72; O, 9.96

Price and Availability

Size Price Availability Quantity
100mg USD 350.00 2 weeks
250mg USD 550.00 2 weeks
1g USD 950.00 2 weeks
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Related CAS #
No Data
Synonym
DICA; Diclondazolic acid; Doridamina; AF 1890; AF1890; AF-1890; Lonidamine
IUPAC/Chemical Name
1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid
InChi Key
WDRYRZXSPDWGEB-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H10Cl2N2O2/c16-10-6-5-9(12(17)7-10)8-19-13-4-2-1-3-11(13)14(18-19)15(20)21/h1-7H,8H2,(H,20,21)
SMILES Code
O=C(C1=NN(CC2=CC=C(Cl)C=C2Cl)C3=C1C=CC=C3)O
Appearance
Solid powder
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Lonidamine (AF-1890) is a hexokinase and mitochondrial pyruvate carrier inhibitor (Ki: 2.5 μM).
In vitro activity:
In isolated mitochondria, LND (lonidamine) causes the dissipation of the mitochondrial inner transmembrane potential and the release of apoptogenic factors capable of inducing nuclear apoptosis in vitro. Thus the mitochondrion is the subcellular target of LND. All effects of LND on isolated mitochondria are counteracted by cyclosporin A, an inhibitor of the mitochondrial PT pore. Reference: Oncogene. 1999 Apr 22;18(16):2537-46. https://pubmed.ncbi.nlm.nih.gov/10353597/
In vivo activity:
LND (lonidamine) potently inhibits MPC activity in isolated rat liver mitochondria (Ki2.5 μM) and co-operatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevisoocytes with K0.5 and Hill coefficient values of 36-40 μM and 1.65-1.85 respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50~ 7 μM) than other substrates including glutamate (IC50~ 20 μM). Reference: Biochem J. 2016 Apr 1;473(7):929-36. https://pubmed.ncbi.nlm.nih.gov/26831515/
Solvent mg/mL mM
Solubility
DMF 25.0 77.84
DMF:PBS (pH 7.2) (1:1) 0.5 1.56
DMSO 41.5 129.31
Ethanol 1.7 5.15
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 321.16 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Ravagnan L, Marzo I, Costantini P, Susin SA, Zamzami N, Petit PX, Hirsch F, Goulbern M, Poupon MF, Miccoli L, Xie Z, Reed JC, Kroemer G. Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore. Oncogene. 1999 Apr 22;18(16):2537-46. doi: 10.1038/sj.onc.1202625. PMID: 10353597. 2. Del Bufalo D, Biroccio A, Soddu S, Laudonio N, D'Angelo C, Sacchi A, Zupi G. Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene. J Clin Invest. 1996 Sep 1;98(5):1165-73. doi: 10.1172/JCI118900. PMID: 8787680; PMCID: PMC507539. 3. Yin X, Choudhury M, Kang JH, Schaefbauer KJ, Jung MY, Andrianifahanana M, Hernandez DM, Leof EB. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β. Sci Signal. 2019 Dec 17;12(612):eaax4067. doi: 10.1126/scisignal.aax4067. PMID: 31848318. 4. Nancolas B, Guo L, Zhou R, Nath K, Nelson DS, Leeper DB, Blair IA, Glickson JD, Halestrap AP. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016 Apr 1;473(7):929-36. doi: 10.1042/BJ20151120. Epub 2016 Feb 1. PMID: 26831515; PMCID: PMC4814305.
In vitro protocol:
1. Ravagnan L, Marzo I, Costantini P, Susin SA, Zamzami N, Petit PX, Hirsch F, Goulbern M, Poupon MF, Miccoli L, Xie Z, Reed JC, Kroemer G. Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore. Oncogene. 1999 Apr 22;18(16):2537-46. doi: 10.1038/sj.onc.1202625. PMID: 10353597. 2. Del Bufalo D, Biroccio A, Soddu S, Laudonio N, D'Angelo C, Sacchi A, Zupi G. Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene. J Clin Invest. 1996 Sep 1;98(5):1165-73. doi: 10.1172/JCI118900. PMID: 8787680; PMCID: PMC507539.
In vivo protocol:
1. Yin X, Choudhury M, Kang JH, Schaefbauer KJ, Jung MY, Andrianifahanana M, Hernandez DM, Leof EB. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β. Sci Signal. 2019 Dec 17;12(612):eaax4067. doi: 10.1126/scisignal.aax4067. PMID: 31848318. 2. Nancolas B, Guo L, Zhou R, Nath K, Nelson DS, Leeper DB, Blair IA, Glickson JD, Halestrap AP. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016 Apr 1;473(7):929-36. doi: 10.1042/BJ20151120. Epub 2016 Feb 1. PMID: 26831515; PMCID: PMC4814305.
1: Shao F, Wang L, Chu X. [Lonidamine induces apoptosis via endoplasmic reticulum stress response and down-regulating cIAP expression in human breast carcinoma MCF-7 cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2015 Jun;35(6):883-7. Chinese. PubMed PMID: 26111690. 2: Cervantes-Madrid D, Romero Y, Dueñas-González A. Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy. Biomed Res Int. 2015;2015:690492. doi: 10.1155/2015/690492. Epub 2015 Sep 6. Review. PubMed PMID: 26425550; PubMed Central PMCID: PMC4575731. 3: Bhutia YD, Babu E, Ganapathy V. Re-programming tumour cell metabolism to treat cancer: no lone target for lonidamine. Biochem J. 2016 Jun 1;473(11):1503-6. doi: 10.1042/BCJ20160068. Review. PubMed PMID: 27234586; PubMed Central PMCID: PMC4888454. 4: Nath K, Guo L, Nancolas B, Nelson DS, Shestov AA, Lee SC, Roman J, Zhou R, Leeper DB, Halestrap AP, Blair IA, Glickson JD. Mechanism of antineoplastic activity of lonidamine. Biochim Biophys Acta. 2016 Dec;1866(2):151-162. doi: 10.1016/j.bbcan.2016.08.001. Epub 2016 Aug 4. Review. PubMed PMID: 27497601; PubMed Central PMCID: PMC5138080. 5: Li N, Zhang CX, Wang XX, Zhang L, Ma X, Zhou J, Ju RJ, Li XY, Zhao WY, Lu WL. Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways. Biomaterials. 2013 Apr;34(13):3366-80. doi: 10.1016/j.biomaterials.2013.01.055. Epub 2013 Feb 11. PubMed PMID: 23410681. 6: Assanhou AG, Li W, Zhang L, Xue L, Kong L, Sun H, Mo R, Zhang C. Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment. Biomaterials. 2015 Dec;73:284-95. doi: 10.1016/j.biomaterials.2015.09.022. Epub 2015 Sep 16. PubMed PMID: 26426537. 7: Nath K, Nelson DS, Heitjan DF, Leeper DB, Zhou R, Glickson JD. Lonidamine induces intracellular tumor acidification and ATP depletion in breast, prostate and ovarian cancer xenografts and potentiates response to doxorubicin. NMR Biomed. 2015 Mar;28(3):281-90. doi: 10.1002/nbm.3240. Epub 2014 Dec 12. PubMed PMID: 25504852; PubMed Central PMCID: PMC4361034. 8: Nath K, Nelson DS, Heitjan DF, Zhou R, Leeper DB, Glickson JD. Effects of hyperglycemia on lonidamine-induced acidification and de-energization of human melanoma xenografts and sensitization to melphalan. NMR Biomed. 2015 Mar;28(3):395-403. doi: 10.1002/nbm.3260. PubMed PMID: 25702942; PubMed Central PMCID: PMC4361035. 9: Davidescu M, Macchioni L, Scaramozzino G, Cristina Marchetti M, Migliorati G, Vitale R, Corcelli A, Roberti R, Castigli E, Corazzi L. The energy blockers bromopyruvate and lonidamine lead GL15 glioblastoma cells to death by different p53-dependent routes. Sci Rep. 2015 Sep 21;5:14343. doi: 10.1038/srep14343. PubMed PMID: 26387611; PubMed Central PMCID: PMC4585687. 10: Coss RA, Storck CW, Wells TC, Kulp KA, Wahl M, Leeper DB. Thermal sensitisation by lonidamine of human melanoma cells grown at low extracellular pH. Int J Hyperthermia. 2014 Feb;30(1):75-8. doi: 10.3109/02656736.2013.858832. Epub 2013 Dec 3. PubMed PMID: 24295212. 11: Zhang BF, Xing L, Cui PF, Wang FZ, Xie RL, Zhang JL, Zhang M, He YJ, Lyu JY, Qiao JB, Chen BA, Jiang HL. Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA and lonidamine. Biomaterials. 2015 Aug;61:178-89. doi: 10.1016/j.biomaterials.2015.05.027. Epub 2015 May 16. PubMed PMID: 26004233. 12: Guo L, Shestov AA, Worth AJ, Nath K, Nelson DS, Leeper DB, Glickson JD, Blair IA. Inhibition of Mitochondrial Complex II by the Anticancer Agent Lonidamine. J Biol Chem. 2016 Jan 1;291(1):42-57. doi: 10.1074/jbc.M115.697516. Epub 2015 Oct 31. PubMed PMID: 26521302; PubMed Central PMCID: PMC4697178. 13: McVicar N, Li AX, Meakin SO, Bartha R. Imaging chemical exchange saturation transfer (CEST) effects following tumor-selective acidification using lonidamine. NMR Biomed. 2015 May;28(5):566-75. doi: 10.1002/nbm.3287. Epub 2015 Mar 23. PubMed PMID: 25808190. 14: Nancolas B, Guo L, Zhou R, Nath K, Nelson DS, Leeper DB, Blair IA, Glickson JD, Halestrap AP. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016 Apr 1;473(7):929-36. doi: 10.1042/BJ20151120. Epub 2016 Feb 1. PubMed PMID: 26831515; PubMed Central PMCID: PMC4814305. 15: Macchioni L, Davidescu M, Roberti R, Corazzi L. The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria. J Bioenerg Biomembr. 2014 Oct;46(5):389-94. doi: 10.1007/s10863-014-9577-5. Epub 2014 Sep 7. PubMed PMID: 25194986. 16: Mruk DD, Bonanomi M, Silvestrini B. Lonidamine-ethyl ester-mediated remodelling of the Sertoli cell cytoskeleton induces phosphorylation of plakoglobin and promotes its interaction with ?-catenin at the blood?testis barrier. Reprod Fertil Dev. 2016 Mar 7. doi: 10.1071/RD15378. [Epub ahead of print] PubMed PMID: 26946288. 17: Schmeisser S, Zarse K, Ristow M. Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species. Horm Metab Res. 2011 Sep;43(10):687-92. doi: 10.1055/s-0031-1286308. Epub 2011 Sep 19. PubMed PMID: 21932172. 18: Calviño E, Estañ MC, Simón GP, Sancho P, Boyano-Adánez Mdel C, de Blas E, Bréard J, Aller P. Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation. Biochem Pharmacol. 2011 Dec 1;82(11):1619-29. doi: 10.1016/j.bcp.2011.08.017. Epub 2011 Aug 27. PubMed PMID: 21889928. 19: Milane L, Duan ZF, Amiji M. Pharmacokinetics and biodistribution of lonidamine/paclitaxel loaded, EGFR-targeted nanoparticles in an orthotopic animal model of multi-drug resistant breast cancer. Nanomedicine. 2011 Aug;7(4):435-44. doi: 10.1016/j.nano.2010.12.009. Epub 2011 Jan 8. PubMed PMID: 21220050; PubMed Central PMCID: PMC3136558. 20: Nath K, Nelson DS, Putt ME, Leeper DB, Garman B, Nathanson KL, Glickson JD. Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice. PLoS One. 2016 Jun 10;11(6):e0157125. doi: 10.1371/journal.pone.0157125. eCollection 2016. PubMed PMID: 27285585; PubMed Central PMCID: PMC4902256.